Objective:To detect the unknown mutation gene and to expand the mutation spectrum by describing a Chinese family with idiopathic hypogonadotropic hypogonadism(IHH). Methods:Clinical information of family members were collected. Second-generation sequencing technology was used to determine the proband’s mutation. Sanger sequencing was used to confirm proband’s mutation results and to detect her parents and younger sister. Results:In the inbreeding family

the proband(25-year-old)showed delayed puberty

primary amenorrhea

infertility

lack of gonadotropins and other typical manifestations of IHH. The proband’s younger brother and sister were also showed delayed puberty. The proband’s parents are cousins and are healthy. Sequencing analysis identified a novel nonsense mutation in exon 5 of the KISS1 R gene(c.C983 A

p. S328X). The proband and her sister were in homozygous state and her parents were in heterozygous state. Conclusion:We have identified a novel homozygous nonsense mutation in the KISS1 R gene causing IHH.